Water insoluble polymer matrix for drug delivery

Abstract

Disclosed is a pharmaceutical composition comprising (a) a bioerodible water insoluble polymer matrix comprising a polyester polymer, wherein the polymer matrix has a melting point of less than 60° C. and (b) an active agent dispersed within the polymer matrix, wherein the composition is formulated to controllably release the active agent for a pre -determined period of time to a target site. Also disclosed are methods of treating a disease or condition with the disclosed compositions.

What is claimed is: 
     
       1. A pharmaceutical composition comprising:
 (a) a bioerodible water insoluble polymer matrix comprising a polyester polymer, wherein the polymer matrix has a melting point of less than 60° C. and wherein the polyester polymer has an average molecular weight of 400 to 4000 and wherein the polyester polymer is at least 80 wt % of the composition; and 
 (b) an active agent dispersed within the polymer matrix; 
 wherein the active agent is an ophthalmic drug and wherein the viscosity of the composition is from 100 to 2000 cps at 55° C. and wherein the composition is formulated to controllably release the active agent within a vitreous of an eye for a pre-determined period of time and wherein the composition is a liquid or paste that can be injected through a needle no larger than 22 gauge into the vitreous without requiring a physical change of the composition. 
 
     
     
       2. The pharmaceutical composition of  claim 1 , wherein the composition comprises a water miscible liquid incorporated in the matrix and wherein the concentration of the water miscible liquid is up to 50% (w/w). 
     
     
       3. The pharmaceutical composition of  claim 2 , wherein the water miscible organic liquid is miscible within the polymer matrix. 
     
     
       4. The pharmaceutical composition of  claim 1 , wherein the polymer matrix comprises a polymer selected from the group consisting of: poly(c-caprolactone)s; poly(ethylene glycol adipate)s; poly(propylene glycol adipate)s; poly(butylene glycol adipate)s; and blends and copolymers thereof. 
     
     
       5. The pharmaceutical composition of  claim 4 , wherein the polymer matrix comprises a poly(ε-caprolactone) polymer. 
     
     
       6. The pharmaceutical composition of  claim 1 , wherein the polymer matrix comprises a polyester polymer selected from the group consisting of: 
       
         
           
           
               
               
           
         
         wherein 
         R 1 , R 2  and R 3  are independently selected from the group consisting of alkyl and alkoxyl diols, triols and tetraols of 2 to 8 carbon atoms; 
         w, w 1  are independently an integer from 4 to 12; 
         W 2 , w 3  are independently an integer from 1 to 12; 
         W 4 , w 5 , w 6 , w 7 , w 8 , w 9  and w 10  are independently an integer from 0 to 12; 
         n is an integer from 4 to 9; and 
         m is an integer from 2 to 8. 
       
     
     
       7. The pharmaceutical composition of  claim 6 , wherein R 1 , R 2  and R 3  are independently selected from the group consisting of butanediol, hexanediol, neopentyl glycol, diethylene glycol, trimethylol propane and pentaerythritol. 
     
     
       8. The pharmaceutical composition of  claim 1 , wherein the polymer matrix comprises a polymer having the formula (C 6 H 10 O 2 ) x .(C 5 H 8 O 4 ) where x is such that the polymer has an average molecular weight of about 1000. 
     
     
       9. The pharmaceutical composition of  claim 1 , wherein the ophthalmic drug has anti-infective or anti-allergic properties. 
     
     
       10. The pharmaceutical composition of  claim 1 , wherein the ophthalmic drug is an ocular hypotensive drug selected from the group consisting of carbonic anhydrase inhibitors; beta-blockers; prostaglandins; bradykinin agonists; rho-kinase inhibitors; C-type natriuretic peptide receptor agonists, and guanylate cyclase activators. 
     
     
       11. A kit comprising the composition of  claim 1  and a syringe. 
     
     
       12. The pharmaceutical composition of  claim 1 , wherein the polyester polymer is at least 85 wt % of the composition. 
     
     
       13. The pharmaceutical composition of  claim 6 , wherein the polyester polymer is at least 85 wt % of the composition. 
     
     
       14. The pharmaceutical composition of  claim 1  wherein the ophthalmic drug is for treatment of age-related macular degeneration. 
     
     
       15. The pharmaceutical composition of  claim 13  wherein the therapeutic agent is an ophthalmic drug for treatment of age-related macular degeneration.